Arenosclerins A−C and Haliclonacyclamine E, New Tetracyclic Alkaloids from a Brazilian Endemic Haplosclerid SpongeArenosclerabrasiliensis

Abstract

Arenosclerins A (2), B (3), and C (4), as well as haliclonacyclamine E (1), are new tetracyclic alkylpiperidine alkaloids isolated from a new species of marine sponge belonging to the order Haplosclerida, Arenosclera brasiliensis, a species endemic to the southeastern Brazilian coast. The alkaloids were isolated as their hydrochloride salts and identified by analysis of spectroscopic data. Data obtained from (1)H-(1)H COSY, HMBC, and HSQC-TOCSY NMR experiments allowed complete assignment of the (1)H and (13)C resonances, and analysis of the NOESY and ROESY spectra showed that the only differences between 2, 3, and 4 were the relative stereochemistries of the bispiperidine ring system. Arenosclerins A-C are the first haliclonacyclamine/halicyclamine-related alkaloids with a hydroxy group in the bridging alkyl chain.

Total Synthesis of (±)‐Haliclonacyclamine C

“…This supported the C7 and C9 relative stereochemistry was identical to haliclonacyclamines A-D. 37 The NOESY spectra also showed clear dipolar couplings between H8b, H6b, and H10b indicating are all axial and on the same face of the piperidine ring ( Figure 11). 37 A dipolar coupling observed between H2 and H10b indicated that the C2/C3 relative stereochemistry was opposite of that observed in the haliclonacyclamines A-D. Other dipolar couplings placed H2, H4a, H6b, H8b, and H10b in an axial orientation and on the same face of the bis-piperidine system. Dipolar couplings observed between H1a and H3, as well as H5a and H3, indicated that H1a, H3, and H5a were all axial.…”

“…37 The first of these new isolates was assigned haliclonacyclamine E (3.6, Figure 10). High resolution mass spectrometry provided the molecular formula C 32 H 55 N 2 , and the 13 C NMR indicated six Throughout their structural analysis the Berlinck group noticed several spectral discrepancies for haliclonacyclamine E (3.6) in comparison to data for haliclonacyclamines A-D. Spectral differences resided in the bis-piperidine core.…”

“…High resolution mass spectrometry provided the molecular formula C 32 H 55 N 2 , and the 13 C NMR indicated six Throughout their structural analysis the Berlinck group noticed several spectral discrepancies for haliclonacyclamine E (3.6) in comparison to data for haliclonacyclamines A-D. Spectral differences resided in the bis-piperidine core. 37 First, the chemical shifts around the core were different. For example, C2 (δ 31.6) in haliclonacyclamine E (3.6) was shielded by 10 ppm compared to haliclonacyclamines A-D (δ between 40.0 and 41.1), C2 (∆δ of +5 ppm in 3.6), C4 (∆δ of -3 ppm in 3.6), C5 (∆δ of +4 ppm in 3.6), and C8 (∆δ of -8 ppm in 3.6).…”

“…Dipolar couplings observed between H1a and H3, as well as H5a and H3, indicated that H1a, H3, and H5a were all axial. 37 Haliclonacyclamine F (3.7)…”

“…Despite the challenges encountered during structure elucidation of tetracyclic 3-alkylpiperidines, Crews, Garson, Berlinck, Kashman, and co-workers have isolated and determined structure for over sixteen tetracyclic alkaloids. [33][34][35][36][37]105,106 This chapter will examine structural differences and the assignment of relatively stereochemistry among this subgroup of 3-alkylpiperidine alkaloids.…”